Dietary glycine blunts liver injury after bile duct ligation in rats.
OBJECTIVE
To investigate the effects of (dietary) glycine against oxidant-induced injury caused by bile duct ligation (BDL).


METHODS
Either a diet containing 5% glycine or a standard diet was fed to male Sprague-Dawley (SD) rats. Three days later, BDL or sham-operation was performed. Rats were sacrificed 1 to 3 d after BDL. The influence of deoxycholic acid (DCA) in the presence or absence of glycine on liver cells was determined by measurement of calcium and chloride influx in cultivated Kupffer cells and lactate dehydrogenase (LDH) activity was determined in the supernatant of cultivated hepatocytes.


RESULTS
Serum alanine transaminase levels increased to about 600 U/L 1 d after BDL. However, enzyme release was blunted by about two third in rats receiving glycine. Release of the alkaline phosphatase and aspartate aminotransferase was also blocked significantly in the group fed glycine. Focal necrosis was observed 2 d after BDL. Glycine partially blocked the histopathological changes. Incubation of Kupffer cells with DCA led to increased intracellular calcium that could be blocked by incubation with glycine. However, systemic blockage of Kupffer cells with gadolinium chloride had no effects on transaminase release. Incubation of isolated hepatocytes with DCA led to a significant release of LDH after 4 h. This release was largely blocked when incubation with glycine was performed.


CONCLUSIONS
These data indicate that glycine significantly decreased liver injury, most likely by a direct effect on hepatocytes. Kupffer cells do not appear to play an important role in the pathological changes caused by cholestasis.
Froh
Matthias
M
Department of Internal Medicine I, University of Regensburg, Regensburg 93042, Germany. froh.science@mac.com.
Zhong
Zhi
Z
Walbrun
Peter
P
Lehnert
Mark
M
Netter
Susanne
S
Wiest
Reiner
R
Conzelmann
Lars
L
Gabele
Erwin
E
Hellerbrand
Claus
C
Scholmerich
Jurgen
J
Thurman
Ronald-G
RG
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000494:pharmacology; D002779:Cholestasis / Q000150:complications* / Q000209:etiology*; D003840:Deoxycholic Acid / Q000494:pharmacology; D004032:Diet; D004195:Disease Models, Animal; D005998:Glycine / Q000008:administration & dosage / Q000627:therapeutic use*; D018684:Glycine Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008026:Ligation / Q000009:adverse effects; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D002712:Chlorides; D002756:Cholagogues and Choleretics; D018684:Glycine Agents; D003840:Deoxycholic Acid; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002118:Calcium; D005998:Glycine